Q14. What other symptoms are associated with Kallmann syndrome ?

Kallmann syndrome and other forms of congenital hypogonadotropic hypogonadism are congenital conditions. This means they are present from birth and have a genetic origin. Over 25 different genes have been found to cause cases of Kallmann syndrome or CHH, with certainly more genes to be discovered. These genes will have other actions around the body and can problems or defects in these genes can lead to additional symptoms.

Every case of Kallmann syndrome or CHH is slightly different, the gene defects in each case might be different. Even if the same gene defects are present they may not cause the same problems in two different cases.

This has given rise to a range of extra symptoms that can sometimes be associated with Kallmann syndrome and CHH. Some are very rare, some are more common. These symptoms will exist in people without Kallmann syndrome or CHH but when they occur in addition to delayed or absent puberty it can alert doctors to a possible diagnosis.

Anosmia or a lack of sense of smell is the defining feature of Kallmann syndrome and is the one symptom that separates Kallmann syndrome from other forms of congenital hypogonadotropic hypogonadism

Cryptorchidism, the failure of one or both of the testes to descend down into the scrotum by birth occurs in a small number of cases. It should be corrected early in life either through drug treatment or surgery or could have a negative impact on the chances of future fertility.

Osteoporosis and osteopenia while not direct symptoms of Kallmann syndrome can develop if oestrogen or testosterone levels have been too low, this can happen if treatment is delayed, stopped or at insufficient levels. Regular DEXA or bone density scans are recommended for Kallmann syndrome patients, along with possibly Vitamin D supplements in order reduce the risk of developing weak or brittle bones.

Gynaecomastia can occur in men with Kallmann syndrome due to an imbalance in the levels of testosterone and oestrogen in body. The prefix gynae- means "women's" and -mastia, "the breasts". It is characterised by partial, female-like enlargement of one or both breasts. Only rarely is this painful and it is generally harmless. If a person is overweight during puberty the condition can sometimes be dismissed as "puppy fat" however if it can be a cause of extreme embarrassment.

All men have traces of the female hormone oestrogen as well as native testosterone in their bodies. Some testosterone is even converted to oestrogen by natural processes. Normally in men the levels of testosterone are so high compared to those of oestrogen that the oestrogen has little discernible effect on the body.

However in conditions such as hypogonadism, as in Kallmann syndrome, where the levels of testosterone are much lower than normally seen in men oestrogen is allowed to have a far greater impact on the body. One result of this is the formation of breast tissue.

Gynaecomastia can sometimes occur with some forms of gonadotropin therapy, especially hCG (Pregnyl) where the dose injected is too high and some of the testosterone formed is converted into oestrogen via a process called aromatisation.

Although gynaecomastia does appear in a few cases of Kallmann's syndrome, the general belief is that it is not really any more common amongst hypogonadal sufferers than it is amongst the normal male population. Even male teenagers going through normal puberty may experience a temporary enlargement of the breasts as sometimes hormone levels take a little longer to stabilise. This is known as pseudogynaecomastia due to excess "puppy fat" and often disappears by the end of puberty. Some overweight men may also appear to have enlarged breast tissue.

Normally the symptoms disappear once testosterone levels have reached the correct level and remain steady. If the symptoms persist drug treatment in the form of anti-aromatase medications might be offered but more often it is corrected by surgery under local or general anaesthetic.

Bimanual synkinesis ('mirror movements') is an uncommon characteristic and is limited to a very particular form of Kallmann syndrome known as x-linked Kallmann syndrome. The term x-linked refers to how the particular case of Kallmann syndrome was inherited. It is not the most common form of Kallmann syndrome, accounting for less than 10% of all Kallmann syndrome cases and not all people with x-linked Kallmann syndrome will have this characteristic.

Bimanual synkinesis also known as mirror movements, literally means "the simultaneous movement of both hands". Mirror movements are observed when one hand involuntary copies the action of the other hand. It can make some activities like playing the piano or climbing a ladder feel a little strange as both hands are "told" by the brain to move in the same way at the same time even when that is not the desired outcome.

Just how and why this characteristic is associated with x-linked Kallmann syndrome is not fully understood and generally does wear off over time.

Shortened fourth metacarpal is a common characteristic of Kallmann syndrome, found in both men and women with the disease. Look at Figure 14a below.

The hand is made up of 27 separate bones, five of which are called the metacarpals, one for each finger. The end of each metacarpal forms a knuckle and counting the thumb as the first finger, the fourth metacarpal is one of the bones making up part of the "ring finger". For some as yet unexplained reason, many people with Kallmann syndrome have fourth metacarpals which are shorter than normal. The remaining fingers are relatively long, another example of the eunuchoidism discussed in a previous answer.

One method to show if somebody has a shortened fourth metacarpal is clench a tight fist with one hand. Then, take a straight object such as a pencil or ruler and lay it across the knuckles of the middle and little fingers. If the fourth metacarpal is shortened the knuckle of the ring finger will not touch, or will only just touch the pencil or ruler (look at Figure 14b).

Unilateral renal agenesis is another rare symptom linked to a specific form of Kallmann syndrome, known as x-linked Kallmann syndrome. Agenesis means "the absence of ", unilateral renal agenesis means the absence of one of the two kidneys.

The kidneys are part of the body's purification system and are responsible for salt balance and to remove waste products out of the body via urine. Often doctors will perform an ultrasound of the kidneys as part of the initial diagnosis of Kallmann syndrome.

People can live perfectly well with just one kidney but if it becomes damaged or malfunctions in some way it can lead to serious problems.

Harelip and cleft palate,along with other facial deformities known as mid-line deformities can be found in cases in Kallmann syndrome but they are by no means unique to Kallmann syndrome and are associated with specific gene defects. Normally they can be corrected with good results by cosmetic surgery. A harelip is a clearly visible division of the upper lip and a cleft palate is a division of the roof of the mouth. A cleft palate often appears together with a harelip.

Colour blindness was original thought to the linked to Kallmann syndrome when the condition was first described. Back in 1944, Franz Kallmann reported that some of his hypogonadal patients were colour blind. However, not all of his patients were anosmic and therefore would not have qualified as having Kallmann syndrome anyway. Now, over fifty years later, it is widely believed that colour blindness is not linked to Kallmann syndrome at all, but rather that Kallmann's original observations were coincidental.